Maryam Zaid

Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan: the NIPPON DATA80 cohort study

Objectives To evaluate the impact of dietary sodium and potassium (Na–K) ratio on mortality from total and subtypes of stroke, cardiovascular disease (CVD) and all causes, using 24-year follow-up data of a representative sample of the Japanese population. Setting Prospective cohort study. Participants In the 1980 National Cardiovascular Survey, participants were followed for 24 years (NIPPON DATA80, National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged). Men and women aged 30–79 years without hypertensive treatment, history of stroke or acute myocardial infarction (n=8283) were divided into quintiles according to dietary Na–K ratio assessed by a 3-day weighing dietary record at baseline. Age-adjusted and multivariable-adjusted HRs were calculated using the Mantel-Haenszel method and Cox proportional hazards model. Primary outcome measures Mortality from total and subtypes of stroke, CVD and all causes. Results A total of 1938 deaths from all causes were observed over 176 926 person-years. Na–K ratio was significantly and non-linearly related to mortality from all stroke (p=0.002), CVD (p=0.005) and total mortality (p=0.001). For stroke subtypes, mortality from haemorrhagic stroke was positively related to Na–K ratio (p=0.024). Similar relationships were observed for men and women. The observed relationships remained significant after adjustment for other risk factors. Quadratic non-linear multivariable-adjusted HRs (95% CI) in the highest quintile versus the lowest quintile of Na–K ratio were 1.42 (1.07 to 1.90) for ischaemic stroke, 1.57 (1.05 to 2.34) for haemorrhagic stroke, 1.43 (1.17 to 1.76) for all stroke, 1.39 (1.20 to 1.61) for CVD and 1.16 (1.06 to 1.27) for all-cause mortality. Conclusions Dietary Na–K ratio assessed by a 3-day weighing dietary record was a significant risk factor for mortality from haemorrhagic stroke, all stroke, CVD and all causes among a Japanese population.

Cross-Sectional Comparison of Coronary Artery Calcium Scores Between Caucasian Men in the United States and Japanese Men in Japan The Multi-Ethnic Study of Atherosclerosis and the Shiga Epidemiological Study of Subclinical Atherosclerosis

The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45-54, 55-64, or 65-74 years). We used community-based samples of Caucasian men in the United States (2000-2002; n = 1,067) and Japanese men in Japan (2006-2008; n = 832) aged 45-74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian mens having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian mens having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45-54, 55-64, and 65-74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups.

Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men

Background Smoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia. Methods and Results In a population‐based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross‐sectional associations of smoking status, cumulative pack‐years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima‐media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle‐brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16–2.79]; CIMT >1.0 mm, 1.88 [1.02–3.47]; AoAC >0, 4.29 [2.30–7.97]; and ankle‐brachial index <1.1, 1.78 [1.16–2.74]) and former smokers did in carotid and aortic circulations (CIMT >1.0 mm, 1.94 [1.13–3.34]; and AoAC >0, 2.55 [1.45–4.49]). Dose–response relationships of pack‐years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle‐brachial index, were observed among both current and former smokers, and even a small amount of pack‐years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices. Conclusions Cigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

Lipoprotein particle profiles compared with standard lipids in association with coronary artery calcification in the general Japanese population

OBJECTIVE The utility of lipoprotein particle profiles measured by nuclear magnetic resonance (NMR) spectroscopy beyond standard serum lipids remains inconclusive. Furthermore, few studies have compared NMR measurements with standard lipids in association with coronary artery calcification (CAC) in Japanese, where the coronary atherosclerotic burden is low. We examined whether NMR-based lipoprotein particle profiles are associated with CAC, and compared them with standard lipid and lipid ratios in the Japanese general population. METHODS AND RESULTS We conducted a cross-sectional study in 851 men aged 40-79 years without cardiovascular diseases and lipid-lowering therapies. Adjusted odds ratios (ORs) (95% confidence intervals) for the top versus the bottom quartile of NMR-measured particle concentrations were 2.01 (1.24-3.23) for low-density lipoprotein (LDL-P), 1.04 (0.62-1.75) for high-density lipoprotein (HDL-P), 1.82 (1.13-2.95) for very-low-density lipoprotein (VLDL-P), and 1.92 (1.18-3.17) for LDL-P/HDL-P ratio. Similarly adjusted ORs of NMR-measured particle sizes were 0.59 (0.36-0.97) for LDL-P, 0.66 (0.40-1.10) for HDL-P, and 0.67 (0.40-1.12) for VLDL-P. The corresponding ORs were 1.82 (1.14-2.90) for total cholesterol (TC), 2.06 (1.28-3.30) for low-density lipoprotein cholesterol (LDL-C), 0.56 (0.34-0.91) for high-density lipoprotein cholesterol (HDL-C), 2.02 (1.24-3.29) for triglycerides, 2.08 (1.29-3.36) for non-high-density lipoprotein cholesterol (non-HDL-C), 2.27 (1.37-3.78) for TC/HDL-C ratio, and 1.73 (1.06-2.85) for LDL-C/HDL-C ratio. After mutual adjustment for total LDL-P concentration and TC/HDL-C ratio or non-HDL-C, LDL-P was no longer associated, whereas TC/HDL-C ratio remained significantly associated with CAC. CONCLUSIONS In community-based Japanese men, the overall association of CAC with NMR-measured lipoprotein indices is comparable, but not superior, to that with standard lipids.

Relationship of Insulin Resistance to Prevalence and Progression of Coronary Artery Calcification Beyond Metabolic Syndrome Components: Shiga Epidemiological Study of Subclinical Atherosclerosis

Objective—The association between insulin resistance (IR) and coronary artery calcification (CAC) has been uncertain after adjustment for metabolic syndrome components. We aimed to evaluate whether IR is associated with CAC prevalence or progression independently of metabolic syndrome components. Approach and Results—We conducted a population-based study in a random sample of Japanese men aged 40 to 79 years and determined IR using the homeostasis model assessment of insulin resistance (HOMA-IR). The associations of HOMA-IR and other diabetic parameters per 1-SD increase with CAC prevalence and progression were evaluated using multivariable logistic regression. Of 1006 total participants at baseline (mean age, 64±10 years), CAC prevalence was observed in 646 (64.2%), and of 789 participants at follow-up (mean duration, 4.9±1.3 years), CAC progression was observed in 365 (46.3%). After adjustment for covariates including metabolic syndrome components, higher HOMA-IR was independently associated with CAC prevalence (adjusted odds ratio 1.34, 95% confidence interval 1.10–1.63; P=0.003) and progression (odds ratio 1.32, 95% confidence interval 1.09–1.60; P=0.004). In participants without diabetes mellitus, positive associations were similarly observed (prevalence: odds ratio 1.29, 95% confidence interval 1.04–1.60; P=0.022; and progression: odds ratio 1.25, 95% confidence interval 1.01–1.55; P=0.042), whereas glucose and hemoglobin A1c were not associated with CAC prevalence and progression. Conclusions—Higher IR was associated with CAC prevalence and progression independently of metabolic syndrome components in Japanese men and also in those without diabetes mellitus. Among diabetic measures, IR and fasting insulin, but not glucose and hemoglobin A1c, predicted CAC progression in men without diabetes mellitus.

Association between Pulse Wave Velocity and Coronary Artery Calcification in Japanese men.

AIM Pulse wave velocity (PWV) is a simple and valid clinical method for assessing arterial stiffness. Coronary artery calcification (CAC) is an intermediate stage in the process leading to overt cardiovascular disease (CVD) and an established determinant of coronary artery disease. This study aimed to examine the association between PWV and CAC in a population-based sample of Japanese men. METHODS This is a cross-sectional study of 986 randomly selected men aged 40-79 years from Shiga, Japan. CVD-free participants were examined from 2006 to 2008. Brachial-ankle PWV (baPWV) was measured using an automatic waveform analyzer. CAC was assessed using computed tomography. Agatston scores ≥ 10 were defined as the presence of CAC. RESULTS Prevalence of CAC progressively increased with rising levels of baPWV: 20.6%, 41.7%, 56.3%, and 66.7% across baPWV quartiles ＜ 1378, 1378-1563, 1564-1849, and ＞ 1849 cm/s (P ＜ 0.001 for trend). Associations remained significant after adjusting for age and other factors, including body mass index, systolic blood pressure, pulse rate, total and high-density lipoprotein cholesterol, hemoglobin A1c, drinking, smoking and exercise status, and the use of medication to treat hypertension, dyslipidemia and diabetes (P=0.042 for trend). The optimal cutoff level of baPWV to detect CAC was 1612 cm/s using receiver operating characteristic curve analysis. CONCLUSIONS Arterial stiffness as defined by an elevated baPWV is associated with an increased prevalence of CAC in a general population-based setting among Japanese men.

Coronary Artery Calcium and Carotid Artery Intima Media Thickness and Plaque: Clinical Use in Need of Clarification

Atherosclerosis begins in early life and has a long latent period prior to onset of clinical disease. Measures of subclinical atherosclerosis, therefore, may have important implications for research and clinical practice of atherosclerotic cardiovascular disease (ASCVD). In this review, we focus on coronary artery calcium (CAC) and carotid artery intima-media thickness (cIMT) and plaque as many population-based studies have investigated these measures due to their non-invasive features and ease of administration. To date, a vast majority of studies have been conducted in the US and European countries, in which both CAC and cIMT/plaque have been shown to be associated with future risk of ASCVD, independent of conventional risk factors. Furthermore, these measures improve risk prediction when added to a global risk prediction model, such as the Framingham risk score. However, no clinical trial has assessed whether screening with CAC or cIMT/plaque will lead to improved clinical outcomes and healthcare costs. Interestingly, similar levels of CAC or cIMT/plaque among various regions and ethnic groups may in fact be associated with significantly different levels of absolute risk of ASCVD. Therefore, it remains to be determined whether measures of subclinical atherosclerosis improve risk prediction in non-US/European populations. Although CAC and cIMT/plaque are promising surrogates of ASCVD in research, we conclude that their use in clinical practice, especially as screening tools for primary prevention in asymptomatic adults, is premature due to many vagaries that remain to be clarified.

Significant inverse association of equol-producer status with coronary artery calcification but not dietary isoflavones in healthy Japanese men

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol >83 nm. The presence of CAC was defined as a coronary Ca score ≥10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 512·7 (interquartile range (IQR) 194·1, 1170·0), 9·1 (IQR 0·10, 33·1) and 0·0 (IQR 0·0, 1·0) nm, respectively. Prevalence of CAC and equol-producers was 9·6 and 16·0 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 0·10 (95 % CI 0·01, 0·90, P<0·04). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.

Self-reported Sleep Duration and Subclinical Atherosclerosis in a General Population of Japanese Men

Aim: There are few data regarding associations between sleep duration and subclinical atherosclerosis in Japan. The aim of this study was to evaluate associations of self-reported sleep duration with calcification in the coronary arteries (CAC) and carotid intima media thickness (IMT) in Japanese men. Methods: This was a cross-sectional survey of 1093 randomly selected men from Kusatsu City, Japan. Average sleep duration on weekdays was estimated through questionnaire; CAC by computed tomography; and carotid IMT by ultrasonography. Results: The prevalence of CAC was 50.0% for participants with sleep duration < 5.5 h, 43.9% with 5.5–6.4 h, 50.0% with 6.5–7.4 h, 49.3% with 7.5–8.4 h, and 62.5% with ≥ 8.5 h. In univariate analysis, participants with sleep duration ≥ 8.5 h had significantly higher prevalence of CAC than those with 6.5–7.4 h (p = 0.043). After adjustment for age and other risk factors, however, the association was not significant (p = 0.776). The average IMT was 0.85 mm for participants with sleep duration < 5.5 h, 0.83 mm with 5.5–6.4 h, 0.85 mm with 6.5–7.4 h, 0.88 mm with 7.5–8.4 h, and 0.90 mm with ≥ 8.5 h. None of the differences in IMT observed in crude or multivariable-adjusted analyses was significant (all p > 0.1). Conclusion: Self-reported sleep duration was not associated with increased CAC or carotid IMT in a general population of Japanese men.

Relationship of serum irisin levels to prevalence and progression of coronary artery calcification: A prospective, population-based study

BACKGROUND The mechanisms by which exercise reduces the risk of coronary heart disease remain poorly understood. Irisin, an exercise-induced polypeptide secreted from skeletal muscles, is proposed to potentially mediate beneficial effects of exercise, especially in metabolic regulation and development of atherosclerosis. We examined whether higher serum irisin levels are associated with lower prevalence and progression of coronary atherosclerosis. METHODS AND RESULTS We performed a prospective, population-based study of Japanese men aged 40-79 years without known coronary heart disease. We measured baseline serum irisin levels using an enzyme-linked immunosorbent assay and quantified coronary artery calcification (CAC) from serial computed tomography scans. Of 1038 participants (mean age, 63.9 years) at baseline, 670 (64.6%) had prevalent CAC. Of 810 participants at follow-up (median, 5.1 years), 407 (50.3%) experienced CAC progression. In Poisson regression with robust error variance adjusted for age and behavioral factors, serum irisin levels were inversely associated with CAC prevalence (relative risk [RR] of 4th versus 1st quartiles [95% confidence interval], 0.88 [0.78-0.99]; trend P = 0.016) and CAC progression (RR, 0.76 [0.63-0.91]; trend P = 0.002). After further adjustment for cardiometabolic risk factors, the inverse association with CAC prevalence disappeared (RR, 0.95 [0.84-1.08]; trend P = 0.319), but that with CAC progression persisted (RR, 0.77 [0.64-0.93]; trend P = 0.003). These associations were consistent when we applied ordinal logistic regression and across subgroups by cardiometabolic risk factor status. CONCLUSIONS Higher serum irisin levels were associated with less burden of coronary atherosclerosis. This association would be mediated through and beyond traditional cardiometabolic pathways.